The invention relates to methods in synthetic carbohydrate chemistry.
Carbohydrates or sugars are the most abundant class of organic compounds found in nature. They are also commercially important, especially in the food and drug industries.
Carbohydrates are divided into three classes of compounds: (1) monosaccharides or simple sugars such as glucose, fructose and galactose, which consist of a single saccharide unit; (2) disaccharides and oligosaccharides such as sucrose (glucose+fructose) or lactose (galactose+glucose), which consist of 2-10 saccharide units linked together; and (3) polysaccharides such as starch and cellulose, which have thousands of saccharide units linked together.
Monosaccharides are classified as aldoses, which in their straight chain form are aldehydes, and ketoses, which are ketones in their straight chain form. While a ketose forms a ring structure which has a hemiketal linkage, an aldose forms a ring structure which has a hemiacetal linkage. ##STR1## For example, the aldose glucose forms the acetal, glucopyranose. ##STR2## The carbonyl or hemiacetal carbon [carbon (1)] in aldoses is called the anomeric carbon. Disaccharides and oligosaccharides are formed when the anomeric carbon on one sugar molecule reacts with the hydroxyl group of another sugar molecule, or other alcohol, to form a glycosidic bond. The glycosidic bond may be .alpha.- or .beta.- depending on the stereochemistry about the anomeric carbon.
Glycosides of aldoses and ketoses have the structure of acetals and ketals, respectively. ##STR3##
The oligosaccharides play key biological roles in humans. They are part of the glycoproteins which form the cell membrane in many tissues. In the last decade, it has become apparent that it is the "glyco" (i.e., the complex sugar) moiety rather than the "protein" moiety of glyoproteins that is of immunological importance. In addition, sugars are also important constituents of the nucleotides of deoxyribonucleic acids (DNA) and ribonucleic acids (RNA). The backbone of DNA and RNA is an alternating chain of pentose (sugar) and phosphate groups, to which purine and pyrimidine bases are attached.
The synthesis of complex sugars by linking one or more monosaccharide units together is of obvious importance to both academic and industrial chemistry. Glycosidation, a reaction of critical importance to all phases of carbohydrate chemistry, is the process of forming a glycoside (4) from a sugar molecule (1) (see reaction scheme below). In glycosidation reactions, the anomeric carbon must be converted into an electrophile, which requires activation by development of a good leaving group (--X or --OH.sub.2) in order to generate a cyclic oxo-carbenium ion (3). ##STR4## The problem encountered in this synthetic route is that it is difficult to perform other chemical transformations at other sites in the saccharide molecule. Such transformations cannot be carried out after the leaving group, --X or --OH.sub.2, is formed at the anomeric carbon because the activated saccharide (2) is sensitive to most chemical reagents that would be used to accomplish transformations at other sites in the molecule. On the Other hand, if the leaving group is formed after such other transformations are performed, the other functionalities may be destroyed in the process of forming the leaving group.